Search PubMed⌕ Search

Biomedical subjects

M Zaider

Publications and source records attributed to M Zaider.

At least 73 records · Page 4Linked to original sources
PubMed1993

A mathematical formalism describing the yield of radiation-induced single- and double-strand DNA breaks, and its dependence on radiation quality.

The purpose of this paper is to describe mathematically the observed dependence of the number of DNA single-strand breaks (SSBs) per unit dose on radiation quality (e.g., LET) by invoking the concept of matrix saturation (i.e., the fact that a nucleotide can be the site of one SSB only and therefore further local energy deposition is wasted), and to show that, based on this, one obtains a characteristic variation of the yield of DNA double-strand breaks with variation of LET, in qualitative agreement with certain experimental determinations. The formalism developed here makes use of methodology from the field of integral geometry, introduced by Kellerer [Radiat. Prot. Dosim. 31, 9-16, 1990] in microdosimetry.

DNA↗
PubMed1992

Compound dual radiation action. I. General aspects.

The theory of dual radiation action (A. M. Kellerer and H. H. Rossi, Curr. Top. Radiat. Res. Q. 8, 85-158, 1972) has attributed the effects of ionizing radiation on eukaryotes to the production of molecular changes (sublesions) that combine pairwise to produce injury (lesions) responsible for radiation effects. If the yield of sublesions is independent of radiation quality (as is currently assumed), dual radiation action results in the well-known proportionality between the average yield of lesions and alpha D+beta D2, where beta is a radiation-independent quantity. It has, however, been observed that beta changes with radiation type. In this paper we propose an explanation of this discrepancy. Specifically, we suggest that dual radiation action-type processes where beta is variable are the result of a mechanism--termed compound dual radiation action--which consists of a sequence of simple dual radiation action processes, each process being the causative agent for the next one. The sequence, single-strand DNA breaks, double-strand DNA breaks (chromosome breaks), and exchange-type chromosomal aberrations, is one such example examined in the paper.

Chromosome Aberrations↗
PubMed1992

On the question of RBE reversal at high doses.

We present theoretical arguments to explain observations of a "reversal" of the RBE at relatively large doses; that is, the RBE of high-LET vs low-LET radiation is less than one. Numerical examples are given and the results of Bogo et al. (Radiat. Res. 118, 341-352, 1989) are discussed qualitatively.

Dose-Response Relationship, Radiation↗
PubMed1991

Charged-particle transport in the condensed phase.

Traditionally, studies of the biological effects of ionizing radiation have rested on the triumvirate: (gas-phase) radiation physics, biophysical modeling, and radiation biology. Two technical developments, the advent of supercomputing as a routine tool in quantum solid-state material science and molecular dynamics on the one hand, and molecular biology on the other hand, have created--perhaps for the first time-the possibility of directly linking a more realistic description of the radiation field to observable events at biomolecular level. It also becomes increasingly clear that the identification of specific molecular targets imposes a challenge to the radiation physics community to be equally specific in treating the energy--deposition stage of radiation action. In this paper: a) I review--and exemplify with results from our own work--the current status in Monte Carlo simulation of gas-phase material (particle transport and stochastic chemistry); b) examine the link between these essentially geometric representations of the track and the concept of "spatial distribution of energy deposition," a staple in radiation modeling; c) advocate an effort towards developing conceptually and calculationally, the field of solid-state microdosimetry; and d) describe methods based on semi-empirical Hamiltonians or quasi-particle techniques for obtaining the frequency-dependent and wave-vector-dependent dielectric response function for biomolecular crystalline systems, which are the main ingredients for describing charged-particle transport.

Mathematics↗
PubMed1991

Evidence of a neutron RBE of 70 (+/- 50) for solid-tumor induction at Hiroshima and Nagasaki and its implications for assessing the effective neutron quality factor.

Carcinogenic and genetic effects in the cohort of A-bomb survivors are the main source of information on radiation effects on humans. A detailed analysis of the age-specific mortality rates for solid tumors as a group using the widely accepted linear-quadratic cum cell-killing dose-effect model reveals that the Hiroshima-Nagasaki data are statistically consistent with a limiting, low-dose neutron RBE of about 70. This value, although consistent with a wide range of neutron RBEs, is about 3.5 times higher than the current effective quality factor for neutrons. The data on leukemia mortality do not support the notion of a difference in effectiveness between neutron and gamma radiation; however, these two radiation sources appear to act synergistically. For both types of tumors, the commonly used concepts of constant, dose-independent RBE and "gamma effective dose" cannot be justified other than at very low neutron doses.

Humans↗
PubMed1990

The relative biological effectiveness of photon radiation from encapsulated iodine-125, assessed in cells of human origin: I. Normal diploid fibroblasts.

The relative biological effectiveness (RBE) of photon radiation from encapsulated Iodine-125 "seed" sources has not previously been investigated in human cells. The RBE of 125I photons relative to 137Cs gamma rays was examined in normal diploid human fibroblasts derived from lung and skin. The cells were irradiated in plateau phase using a specially designed incubator-irradiator which permitted simultaneous 125I and 137Cs irradiation. The cells were irradiated at various dose rates ranging from 7 to 70 cGy/hr. Dosimetry was performed using Monte Carlo computer calculations to simulate the 125I irradiations and the exposure-standardization measurements made by the U.S. National Bureau of Standards which are the basis for the specified strengths of 125I seeds. Simulation of the exposure standardization measurements revealed systematic errors due to the unrecognized presence of low-energy fluorescence X rays. The specified activity of the type of seeds used for this study (high-activity, no radiographic marker) was found to be too high by more than 10%. The RBE of 125I assessed with both lung fibroblast lines was found to be 1.2 and was 1.3 for the skin fibroblasts. The RBE did not change over the range of dose rates tested. In fact, for both 125I and 137Cs, the dose response curves did not change with dose rate over the range tested, implying full repair of sublethal damage at dose rates below 70 cGy/hr in these non-dividing cells.

Brachytherapy↗
PubMed1990

Concepts for describing the interaction of two agents.

This paper reviews general concepts for understanding the effects of two or more agents. Models describing exposures to mixed fields of radiation are developed on the basis of very general postulates, and some of their consequences are examined against a set of experimental data.

Cell Survival↗
PubMed1990

Microdosimetry and Katz's track structure theory. I. One-hit detectors.

A microdosimetric treatment of the response of one-hit detectors to radiation is formulated and compared with the model proposed by R. Katz, S. C. Sharma, and M. Homayoonfar (in Topics in Radiation Dosimetry, Suppl. I (F. H. Attix, Ed.), pp. 317-383, Academic Press, New York, 1972) within the framework of their track-structure theory. It is shown that radial dose distributions (on which the track structure theory is based) are generally poor substitutes for the exact microdosimetric distributions except when (a) the target is much larger than the radial extent of the track or (b) the "effective" specific energy in the target (alpha z, see text) is negligibly small. Since neither one of these conditions is generally satisfied, it is suggested that a meaningful search for one-hit detectors be based on a microdosimetric description of the stochastics of energy deposition. An analysis of the phi x-174 bacteriophage inactivation data is presented.

Mathematics↗
PubMed1989

Ozone activates transforming genes in vitro and acts as a synergistic co-carcinogen with gamma-rays only if delivered after radiation.

An earlier study indicated that ozone (O3), a major pollutant in our atmosphere, acts as a carcinogen as well as a synergistic co-carcinogen with radiation in cultured hamster embryo cells and in mouse C3H10T1/2 cells. In this investigation we further characterize the oncogenic action of ozone, alone or in combination with radiation, on C3H10T1/2 cells with particular emphasis on transformation produced by different temporal patterns of dose delivery of these two agents and low dose effects. We report that ozone-induced transformation involves the activation of dominant transforming genes, thereby indicating that DNA is a target in ozone induced carcinogenesis. We also report that ozone (5 p.p.m. for 5 min) acts as a synergistic co-carcinogen only if delivered after radiation (4 Gy or gamma-rays); when cells are exposed to ozone prior to radiation no enhanced rates of transformation are observed. Our findings also show that ozone at a low dose of 1 p.p.m. (for 5 min) does not act as a carcinogen but does interact as a co-carcinogen with ionizing radiation. The data indicate that the dose and sequence in which ozone and radiation are delivered have important implications for the putative carcinogenic effects of these two agents, a factor that heretofore has not been recognized.

Animals↗
PubMed1989

Estimation of the quality factor on the basis of multi-event microdosimetric distributions.

The measurement of microdosimetric distributions for the purpose of estimating the quality factor, Q, may be encumbered in pulsed radiation fields--as produced, for instance, by accelerators with low duty cycle--because of a signal pile-up. We propose a method of estimating Q from the first several moments of multi-event distributions. In addition to overcoming the high dose-rate problems, the measurement of such distributions can be performed in significantly smaller volumes than conventional microdosimetry, thus raising the possibility of reducing the site diameter (presently 1 micron) for which y in the function Q(y) is specified.

Radiation Dosage↗
PubMed1989

Changes in biological effectiveness of the neutron beam at Clatterbridge (62 MeV p on Be) measured with cells in vitro.

Chinese hamster V79 cells have been used to assess changes in RBE of the p(62)Be neutron beam at the Clatterbridge Hospital with depth in a phantom and with use of a hydrogenous filter. The cells were exposed at depths of 2 and 12 cm and at a depth of 2 cm with a hydrogenous filter. Two groups of experimenters each conducted two experiments. The ratios of relative biological effectiveness (RBE) at a depth of 12 cm to that at 2 cm were found by the two groups to be 0.99 +/- 0.04 and 0.96 +/- 0.02 (standard errors). The effect of a polythene filter 4.5 cm thick was measured at a depth of 2 cm and the ratio of RBE with and without the filter was found by both groups to be 0.99 +/- 0.02. All the experiments suggest that there may be small effects of beam hardening by depth and filtration but these results are in marked contrast with those obtained using an in vivo system.

Animals↗
PubMed1988

On the possibility of obtaining non-diffused proximity functions from cloud-chamber data: I. Fourier deconvolution.

A mathematical procedure, using Fourier deconvolution, is described whereby diffusion-free proximity functions can be obtained from cloud-chamber data. Such non-diffused distributions can be used to obtain further microdosimetric and nanodosimetric quantities hitherto not available from experiments, thus making the cloud chamber an almost ideal nanodosimeter.

Fourier Analysis↗
PubMed1988

On the possibility of obtaining non-diffused proximity functions from cloud-chamber data: II. Maximum entropy and Bayesian methods.

Maximum entropy and Bayesian methods are applied to an inversion problem which consists of unfolding diffusion from proximity functions calculated from cloud-chamber data. The solution appears to be relatively insensitive to statistical errors in the data (an important feature) given the limited number of tracks normally available from cloud-chamber measurements. It is the first time, to our knowledge, that such methods are applied to microdosimetry.

Bayes Theorem↗
PubMed1988

Oncogenic transformation by charged particles of defined LET.

Neoplastic transformation incidence and cytotoxicity were scored in the C3H/10T1/2 cell system following irradiation with charged particles of defined linear energy transfer (LET) produced at the Radiological Research Accelerator Facility of Columbia University. Cells cultured in monolayers, attached to thin Mylar sheets, were irradiated with accelerated protons, deuterons or helium-3 ions, and the results compared with X-rays. Defined LET values obtained by using the track segment mode, ranged from 10 to 120 keV/microns. For X-rays, and for the charged particles of lower LET, the dose-response curves for cell survival have a marked initial shoulder. With increasing LET, there is a progressive decrease in the size of the shoulder and for the highest LETs, survival curves approximate an exponential function of dose. The transformation incidence, likewise, showed a direct correlation to LET over the dose range examined. The efficiencies of transformation, however, appeared to approach a plateau between 80 and 120 keV/micron. Transformation data were analyzed using a linear-quadratic function of dose for the transformation probability. This latter quantity, when analyzed using microdosimetric consideration, suggests that the target volume for this end point is of the order of micrometer.

Animals↗
PubMed1988

The biophysical stage of radiation carcinogenesis.

The dependence of the induction of cancer on the absorbed dose of ionizing radiations has been specified in terms of increasing complexity. The first notion of simple proportionality (the "linear hypothesis") is now frequently replaced with a dependence of both the first and second powers of the dose (the "linear-quadratic model"), which implies proportionality at low doses only. Microdosimetric considerations, in particular the theory of dual radiation action, would be in accord with this relation if tumors were to arise from single cells as the result of a transformation that is autonomous (i.e., depends only on the radiation received by the cell). In this case, it must be expected that the linear portion of the dose-effect curve is dose rate independent, but that the quadratic component may decrease with decreasing dose rate because of repair during the interval between two events (energy depositions by individual particles). Various data appeared to be in agreement with this picture. However, it was shown some time ago that the dose-incidence relation of some neoplasms indicates a non-autonomous response because of departure from a linear dependence when the mean number of events in cells is much less than one in neutron irradiations. Another discrepancy is the repeated observation that reduction of dose rate, while resulting in the expected lessening of the effectiveness of low-LET radiation, increases the effectiveness of neutrons (especially in the case of oncogenic cell transformation). As will be shown, it is possible to account for this phenomenon, although at this point the limitations of the available data make the explanation semi-quantitative and therefore still somewhat hypothetical. However, it should be noted that it does not even require a nonautonomous response and thus is at least an example of the complexities that can arise in the earliest (biophysical) stage of radiation carcinogenesis.

Animals↗
PubMed1988

Microdosimetry near the trajectory of high-energy heavy ions.

Single-event energy distributions were measured in a 1.3-micron-diameter site as a function of radial distance from the trajectory of high-energy iron ions having an energy of about 600 MeV/amu. It was found that beyond distances of a few micrometers the average lineal energy of the (mostly single) secondary electrons (delta rays) is of the order of 3 keV/micron. This is similar to the value found in a medium irradiated by 170-keV photons. The frequency-mean specific energy for delta rays occurring at large distances from the path of the primary ion exceeds the calculated (radial) absorbed dose by two orders of magnitude.

Ions↗